A time-of-flight mass spectrometer is a widely used tool of analytical chemistry, characterized by a high speed of analysis in a wide mass range. It has been recognized that multi-reflecting time-of-flight mass spectrometers (MR-TOF-MS) provide a substantial increase in resolving power due to the flight path extension provided by using multiple reflections between ion optical elements. Such extension in flight path requires folding ion paths either by reflecting ions in ion mirrors, e.g., as described in GB 2080021, or by deflecting ions in sector fields, e.g., as described in Toyoda et al., J. Mass Spectrometry 38 (2003) 1125. MR-TOF-MS instruments that use ion mirrors provide an important advantage of larger energy and spatial acceptance due to high-order time-per-energy and time-per-spatial spread ion focusing.
While MR-TOF-MS instruments fundamentally provide an extended flight path and high resolution, they do not conventionally provide adequate sensitivity since the orthogonal accelerators used to inject ions into the flight path cause a drop in duty cycle at small size ion packets and at extended flight times.
SU 1725289 introduced a folded path planar MR-TOF-MS instrument of the type shown in FIG. 1. The instrument comprises two two-dimensional gridless ion mirrors 12 extended along a drift Z-direction for reflecting ions, an orthogonal accelerator 13 for injecting ions into the device, and a detector 14 for detecting the ions. For clarity, throughout this entire text the planar MR-TOF-MS instrument is described in the standard Cartesian coordinate system. That is, the X-axis corresponds to the direction of time-of-flight, i.e. the direction of ion reflections between the ion mirrors. The Z-axis corresponds to the drift direction of the ions. The Y-axis is orthogonal to both the X and Z axes.
Referring to FIG. 1, in use, ions are accelerated by accelerator 13 towards one of the ions mirrors 12 at an inclination angle α to the X-axis. The ions therefore have a velocity in the X-direction and also a drift velocity in the Z direction. The ions are continually reflected between the two ion mirrors 12 as they drift along the device in the Z-direction until the ions impact upon detector 14. The ions therefore follow a zigzag (jigsaw) mean trajectory within the X-Z plane. The ions advance along the Z-direction per every mirror reflection with an increment ZR=C*sin α, where C is the flight path between adjacent points of reflection in the ion mirrors. However, no ion focusing is provided in the drift Z-direction and so the ion packets diverge in the drift Z-direction. It is theoretically possible to introduce low divergent ion packets between the ion mirrors 12 so as to allow an ion flight path of about 20 m before the ions overlap in the drift Z-direction, thus achieving a mass resolving power between 100000 and 200000. However, in practice it is not possible to inject ions packets into the space between the mirrors 12 that are more than a few millimeters long in the Z-direction without the ions impacting on the orthogonal accelerator 13 as they oscillate in the device. This drawback limits the duty cycle of the spectrometer to less than 0.5% at a mass resolving power of 100,000.
WO 2005/001878 proposes providing a set of periodic lenses within the field-free region so as to overcome the above described problem by preventing the ion beam from diverging in the Z-direction, thus allowing the ion flight path to be extended and the spectrometer resolution to be improved.
WO 2007/044696 further proposes orienting the orthogonal accelerator substantially orthogonal to the ion path plane of the analyzer so as to diminish aberrations of the periodic lenses while improving the duty cycle of the orthogonal accelerator. This technique capitalizes on the smaller spatial Y aberrations of ion mirrors verses the Z-aberrations of the periodic lenses. However, the duty cycle of the orthogonal accelerator is still limited to approximately 0.5% at an analyzer resolution of 100,000.
WO 2011/107836 introduced an alternative approach in order to further improve the duty cycle of the MR-TOF-MS. This approach uses a so-called open trap analyzer, wherein the number of reflections is not fixed, the spectra are composed of signal multiplets corresponding to a range of ion reflections, and the time-of-flight spectra are recovered by decoding of multiplet signals. This configuration allows elongation of both the orthogonal accelerator and the detector, thus enhancing the duty cycle.
Yet further improvement of the orthogonal acceleration duty cycle can be achieved by using frequency encoded pulsing, followed by a step of spectral decoding, as described in WO 2011/107836 and WO 2011/135477. Both of these techniques are particularly suitable for tandem mass spectrometry in combination with a high resolution MR-TOF-MS instrument (e.g., R˜100,000), since the spectral decoding step relies heavily on sparse mass spectral population. However, both of these techniques restrict the dynamic range of MS-only analysers, since spectral population becomes problematic with chemical background noise, occurring at a level of 1E-3 to 1E-4 in major signals.
GB 2476964 and WO 2011/086430 propose curving of ion mirrors in the drift Z-direction, thus forming a hollow cylindrical electrostatic ion trap or MR-TOF analyzer, which allows further extension of the ion flight path for higher mass resolving power and also allows extending the ion packet size in the Z-direction for improving the orthogonal accelerator duty cycle. At much longer flight paths in the cylindrical MR-TOF the mass resolving power is no longer limited by the initial time spread of ion packets, but is rather limited by the aberrations of the analyzer. The aberrations of the flight time (TOF) are primarily due to: (i) ion energy K spread in the flight direction X; (ii) spatial spread of ion packets in the Y-direction; and (iii) spatial spread of ion packets in the drift Z-direction, causing spherical aberration of periodic lenses.
WO 2013/063587 improves the ion mirror isochronicity with respect to energy K and Y-spreads, although the aberration of periodic lenses is the major remaining TOF aberration of the analyzer. In order to reduce those lens aberrations, US 2011/186729 discloses a so-called quasi-planar ion mirror, i.e. a spatially modulated ion mirror field. However, efficient elimination of TOF aberrations in such mirrors can be only be achieved if the period of the electrostatic field modulation in the Z-direction is comparable or larger than the Y-height of the mirror window. This strongly limits the density of ion trajectory folding and flight path extension at practical analyzer sizes. Furthermore, periodic modulation in the Z-direction also affects Y-components of the field, which complicates the analyzer tuning. Thus, the cylindrical analyzer of WO 2011/08643, improved mirrors of WO 2013/063587 and quasi-planar analyzer of US 2011/186729 allow some extension of the orthogonal accelerator length so as to provide a higher duty cycle, but the resource is very limited.
Thus, prior art MR-TOF-MS instruments struggle to provide both high sensitivity and high resolution instruments.
It is desired to provide an improved spectrometer and an improved method of spectrometry.